Rapid, sensitive, and visual detection of swine Japanese encephalitis virus with a one-pot RPA-CRISPR/EsCas13d-based dual readout portable platform.

Japanese encephalitis (JE), a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV), poses a serious threat to global public health. The low viremia levels typical in JEV infections make RNA detection challenging, necessitating early and rapid diagnostic methods for effective control and prevention. This study introduces a novel one-pot detection method that combines recombinant enzyme polymerase isothermal amplification (RPA) with CRISPR/EsCas13d targeting, providing visual fluorescence and lateral flow assay (LFA) results. Our portable one-pot RPA-EsCas13d platform can detect as few as two copies of JEV nucleic acid within 1 h, without cross-reactivity with other pathogens. Validation against clinical samples showed 100 % concordance with real-time PCR results, underscoring the method's simplicity, sensitivity, and specificity. This efficacy confirms the platform's suitability as a novel point-of-care testing (POCT) solution for detecting and monitoring the JE virus in clinical and vector samples, especially valuable in remote and resource-limited settings.

Pickering emulsion gel of polyunsaturated fatty acid-rich oils stabilized by zein-tannic acid green nanoparticles for storage and oxidation stability enhancement.

HYPOTHESIS: Poor storage stability and oxidative deterioration are the common drawbacks of edible oils rich in polyunsaturated fatty acids (PUFAs). We hypothesized that the natural zein/tannic acid self-assembly nanoparticles (ZT NPs) could be employed as stabilizers to anchor at the oil-water interface, thus constructing Pickering emulsion gel (PKEG) system for three types of PUFA-rich oils, soybean oil (SO), fish oil (FO) and cod liver oil (CLO), to improve the storage and oxidation stability. EXPERIMENTS: ZT NPs were prepared by the anti-solvent coprecipitation method, and the three-phase contact angle, FT-IR, and XRD were mainly characterized. To observe the shell-core structure and oil-water interface details of SO/FO/CLO PKEGs by confocal laser scanning microscope and cryo-scanning electron microscope. Accelerated oxidation of FO was performed to assess the protective effect of PKEG on lipids. FINDINGS: The SO, FO, and CLO PKEGs stabilized by 2 % ZT NPs, with oil fraction (φ = 0.5-0.6), were obtained. PKEGs show high viscoelasticity, clear shell-core structure spatial network structure, and ideal storage stability. Under accelerated oxidation, the degree of oxidative rancidity of FO PKEG was obviously lower than that of free FO. Overall, this work opens up new possibilities for using natural PKEG to prevent oxidative deterioration and prolong the shelf-life of PUFA-rich oils.

Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor.

Kisspeptin signaling through its G protein-coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic-pituitary-gonadal axis. Dysregulation of this pathway underlies severe disorders like infertility and precocious puberty. Here, we present cryo-EM structures of KISS1R bound to the endogenous agonist kisspeptin-10 and a synthetic analog TAK-448. These structures reveal pivotal interactions between peptide ligands and KISS1R extracellular loops for receptor activation. Both peptides exhibit a conserved binding mode, unveiling their common activation mechanism. Intriguingly, KISS1R displays a distinct 40° angular deviation in its intracellular TM6 region compared to other Gq-coupled receptors, enabling distinct interactions with Gq. This study reveals the molecular intricacies governing ligand binding and activation of KISS1R, while highlighting its exceptional ability to couple with Gq. Our findings pave the way for structure-guided design of therapeutics targeting this physiologically indispensable receptor.

First Report of Streptomyces brasiliscabiei Causing Common Scab on Potato in China.

Severe typical deep-pitted lesions of Potato Common Scab (PCS) disease were observed in two locations in China, Dingxi, Gansu Province, and Shuozhou, Shaanxi Province, in 2021. Potato farms in Dingxi growing cultivar Huangxin 226 (26 hectares) exhibited a scab disease incidence of 10%, while cultivar Jinshu 15# (4 hectares) in Shuozhou showed a disease incidence of 30% (Fig. 1). During harvest, tubers displaying PCS symptoms were collected for pathogen isolation. To obtain pathogen isolates, surface-sterilized tuber tissue with scab lesions was ground in sterile water, serially diluted, and plated onto ISP5 agar medium plates (Handique et al. 2022). Five pure colonies of Streptomyces isolate were obtained, designated as ZRIMU1503, ZRIMU1502, ZRIMU1320, ZRIMU1321and ZRIMU791. Genomic DNA was extracted and sequenced using Illumina technology. Sequencing data of the 5 isolates were uploaded to NCBI GenBank and annotated (Accession numbers: JBBAYL010000000, JBBAYM010000000, JBBAYN010000000, JBBAYO010000000 and JBBAYP010000000, respectively) using the PGAP pipeline (Tatusova et al. 2016). Average Nucleotide Identity (ANI) values (97.52 %, 97.53 %,97.54 %,97.57 % and 97.52 %, respectively) indicated the identity of the five isolates to the type strain S. brasiliscabiei IBSBF 2867T. Additionally, pairwise comparisons of Digital DNA Hybridization (DDH) value (76.2%, 76.3%, 76.4%, 76.4% and 76.2% respectively) of all the Streptomyces type strains show the highest identity to S. brasiliscabiei IBSBF 2867T. Twelve housekeeping genes (acnA, atpD, dnaN, gap, gyrA, gyrB , infB, mdh, recA, rplB, rpoB, and trpB) were extracted from the genome sequence of the five isolates to construct a multi-locus sequence analysis (MLSA) tree. The evolutionary distance of the five isolates was constructed using MEGAX software (Kumar et al., 1994), along with other Streptomyces strains that are known to cause PCS. The resulting cladogram demonstrated the isolated strains clustered together with S. brasiliscabiei IBSBF 2867T (Fig.2). Koch's postulates were fulfilled by inoculating a perlite potting mix with spore suspensions of each isolate (104 CFU/ml), planting tubers (cv. Favorita), and reproducing PCS symptoms at harvest after three months. Negative control received water treatment. The plants were kept in greenhouse with 12 h of light per day and irrigated regularly. The experiment was repeated twice, once in April 2022 and again in April 2023. On harvest, all five isolates exhibited development of severe symptoms of PCS (Fig.1), while the negative controls had no lesions. The pathogen was reisolated from the lesions and confirmed to be identical to the original isolate by 16S rRNA gene sequences. To our knowledge, this is the first report of S. brasiliscabiei causing PCS in China. S. brasiliscabiei was identified as a new species to cause PCS in Brazil and was identified based on morphology, pathogenicity, and genetic features (Corrêa et al. 2021). Multiple pathogen-causing PCS has been recognized in China and a surge of disease incidence in potato fields has been reported (Handique et al. 2022; Wu et al. 2023). S. brasiliscabiei causes severe symptoms which makes potatoes unmarketable. The disease epidemiology of this pathogen needs to be investigated.

Prognostic analysis of rectal cancer patients after neoadjuvant chemoradiotherapy: different prognostic factors in patients with different TRGs.

PURPOSE: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). METHODS: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. RESULTS: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0-3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792-9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478-2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721-11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535-5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. CONCLUSION: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

MP-3 microperimeter in early primary open angle glaucoma with a new pattern.

AIM: To investigate macular microperimetry in patients with early primary open angle glaucoma (POAG) using a new custom-made pattern, and analyze the characteristics of macular sensitivity. METHODS: This case-control study included 38 patients with POAG, who were divided into pre-perimetric glaucoma (18 eyes of 18 patients), early-stage (20 eyes of 20 patients), and control (20 eyes of 20 patients) groups. All subjects underwent standard 24-2 humphrey visual field test. An MP-3 microperimeter with a new custom-made pattern (28 testing points distributed in four quadrants, covering the central 10° of the retina) was used to evaluate macular sensitivity. Ganglion cell complex (GCC) thicknesses were examined using an RS-3000 Advance OCT system. The features of structure and function were analysed per quadrant. RESULTS: The pre-perimetric glaucoma group had significantly lower inferior hemifield macular sensitivity compared to controls (P<0.05). The early-stage POAG group had significantly lower average, inferior hemifield, inferonasal, and inferotemporal mean sensitivities compared to the pre-perimetric glaucoma group (P<0.05), and lower macular sensitivity in all sectors compared to controls (P<0.05). Regarding GCC thickness, all sectors in the early-stage POAG group became thinner compared to those in controls (P<0.05); whereas all sectors in the early-stage POAG group, except the superonasal quadrant, became thinner compared to those in the pre-perimetric glaucoma group (P<0.05). Macular sensitivity and GCC thickness were significantly associated in each sector. The inferotemporal quadrant had the highest correlation coefficients (0.840). The structure-function relationship for the inferonasal and inferotemporal sectors was stronger compared to the corresponding superior sectors. CONCLUSION: Microperimetry reveals variations in macular sensitivity in patients with early glaucoma earlier than conventional perimetry, particularly in pre-perimetric glaucoma cases in which it might be undetectable by conventional methods. The new custom-made pattern may improve the accuracy of microperimetry by enhancing point arrangement and reducing fatigue effects. Macular sensitivity measured by MP-3 with this pattern shows statistically significant structural and functional associations with the thicknesses of the GCC.

mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Transient Interference Excision and Spectrum Reconstruction with Partial Samples Using Modified Alternating Direction Method of Multipliers-Net for the Over-the-Horizon Radar.

Transient interference often submerges the actual targets when employing over-the-horizon radar (OTHR) to detect targets. In addition, modern OTHR needs to carry out multi-target detection from sea to air, resulting in the sparse sampling of echo data. The sparse OTHR signal will raise serious grating lobes using conventional methods and thus degrade target detection performance. This article proposes a modified Alternating Direction Method of Multipliers (ADMM)-Net to reconstruct the target and clutter spectrum of sparse OTHR signals so that target detection can be performed normally. Firstly, transient interferences are identified based on the sparse basis representation and then excised. Therefore, the processed signal can be seen as a sparse OTHR signal. By solving the Doppler sparsity-constrained optimization with the trained network, the complete Doppler spectrum is reconstructed effectively for target detection. Compared with traditional sparse solution methods, the presented approach can balance the efficiency and accuracy of OTHR signal spectrum reconstruction. Both simulation and real-measured OTHR data proved the proposed approach's performance.

Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (ß: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (ß: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced the risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

Successful Treatment Strategy for Duplicate Inferior Vena Cava and Deep Venous Thrombosis: Filter Placement and Thrombolysis Approach.

BACKGROUND Duplicate inferior vena cava (IVC) accompanied by deep venous thrombosis is rare. The optimal treatment plan is determined according to the results of imaging, including venography. In this report, we present a case of successful treatment of a patient with duplicate IVC and deep venous thrombosis (DVT). CASE REPORT An 84-year-old man with history of hypertension was admitted to the hospital because of 4 days of moderate left lower-limb edema. A thorough examination led to the diagnosis of the DVT. The duplicate IVC was discovered during venography. As the blood from the left common iliac vein mainly flowed to the left IVC, and there were no other communicating branches before the convergence of the left and right IVCs, which was located above the 1st lumbar vertebrae body near the junction of the hepatic vein and the IVC, the strategy of placing only 1 filter in the left inferior vena cava were chosen, rather than placing 1 filter above the confluence of bilateral IVC, or placing a filter in each IVC below the level of renal veins on each side. Following that, the DVT was safely treated with thrombolysis and aspiration without the risk of pulmonary embolism. CONCLUSIONS This case report presented the complete evaluation and management of a patient with lower-limb DVT accompanied by the malformation of duplicate IVC. The filter placement strategy with duplicate IVC in the literature was summarized. We concluded that even in emergency situations, with comprehensive consideration, it is possible to perform endovascular intervention successfully and achieve satisfactory treatment results.

[Analysis and prospect of correlation between relative molecular weight and efficacy of polysaccharides from medicinal plant resources].

Polysaccharides from medicinal plant resources are a kind of polymers extracted from medicinal plants. They are complex long chains formed by different monosaccharides connected via glucosidic bonds. These polysaccharides usually have straight chain and branched chain structures, and their relative molecular weight changes greatly. Modern studies have shown that the biological activi-ty of polysaccharides from medicinal plant resources is closely related to their relative molecular weight. This paper first reviewed the preparation and detection methods of polysaccharides from medicinal plant resources with different relative molecular weights. Then, the paper summarized and analyzed the general experience of the correlation between efficacy and relative molecular weight of polysaccharides from medicinal plant resources with different molecular weights. It was considered that polysaccharides with large relative molecular weights(>100 kDa) play a leading role in immune regulation. Polysaccharides with medium relative molecular weights(10-100 kDa) play a leading role in immune regulation and the protection of the liver. Polysaccharides with small relative molecular weights(<10 kDa) play a leading role in anti-oxidation, regulation of intestinal flora, regulation of blood glucose and lipids, anti-fatigue, and the protection of nerves. Therefore, precise development of polysaccharides from medicinal plant resources based on relative molecular weight is expected to improve their biological activity and application value.

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice.

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism by which sevoflurane activates the NLRP3 inflammasome in microglia remains unclear. The cGAS-STING pathway is an evolutionarily conserved inflammatory defense mechanism. The role of the cGAS-STING pathway in sevoflurane-induced NLRP3 inflammasome-dependent neuroinflammation and the underlying mechanisms require further investigation. We found that prolonged anesthesia with sevoflurane induced cognitive dysfunction and triggered the neuroinflammation characterized by the activation of NLRP3 inflammasome in vivo. Interestingly, the cGAS-STING pathway was activated in the hippocampus of mice receiving sevoflurane. While the blockade of cGAS with RU.521 attenuated cognitive dysfunction and NLRP3 inflammasome activation in mice. In vitro, we found that sevoflurane treatment significantly activated the cGAS-STING pathway in microglia, while RU.521 pre-treatment robustly inhibited sevoflurane-induced NLRP3 inflammasome activation. Mechanistically, sevoflurane-induced mitochondrial fission in microglia and released mitochondrial DNA (mtDNA) into the cytoplasm, which could be abolished with Mdivi-1. Blocking the mtDNA release via the mPTP-VDAC channel inhibitor attenuated sevoflurane-induced mtDNA cytosolic escape and reduced cGAS-STING pathway activation in microglia, finally inhibiting the NLRP3 inflammasome activation. Therefore, regulating neuroinflammation by targeting the cGAS-STING pathway may provide a novel therapeutic target for POCD.

Study on Oxymatrine-Based Research from 2001 to 2022: A Bibliometric Analysis.

Oxymatrine is a quinolizidine alkaloid mainly derived from Kushen; it possesses various therapeutic effects, such as organ- and tissue-protective, anticancer, and antiviral effects. The research directions for oxymatrine remain broad. In order to explore the overall status of oxymatrine-based research, we carried out a bibliometric analysis to summarize the oxymatrine-based, English-written studies published in the past 22 years. In total, 267 studies were included, most of which were original. The number of annual studies slowly increased with some fluctuations. Other than China, 11 different countries conducted studies on oxymatrine; the variety in the country of origin of these publications is presented as a recently increasing trend. Many affiliates and researchers have participated in oxymatrine-based research. Various treatment mechanisms involving different oxymatrine pathways have led to research in a wide range of fields, being published in numerous journals. Two particularly popular research fields related to oxymatrine involved anticancer and anti-inflammation. From this research, we concluded that with increasing and continuous in-depth studies, more therapeutic effects and mechanisms will be elucidated, and oxymatrine may present as a viable option for the treatment of additional diseases.

Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, with many GPCRs having crucial roles in endocrinology and metabolism. Cryogenic electron microscopy (cryo-EM) has revolutionized the field of structural biology, particularly regarding GPCRs, over the past decade. Since the first pair of GPCR structures resolved by cryo-EM were published in 2017, the number of GPCR structures resolved by cryo-EM has surpassed the number resolved by X-ray crystallography by 30%, reaching >650, and the number has doubled every ~0.63 years for the past 6 years. At this pace, it is predicted that the structure of 90% of all human GPCRs will be completed within the next 5-7 years. This Review highlights the general structural features and principles that guide GPCR ligand recognition, receptor activation, G protein coupling, arrestin recruitment and regulation by GPCR kinases. The Review also highlights the diversity of GPCR allosteric binding sites and how allosteric ligands could dictate biased signalling that is selective for a G protein pathway or an arrestin pathway. Finally, the authors use the examples of glycoprotein hormone receptors and glucagon-like peptide 1 receptor to illustrate the effect of cryo-EM on understanding GPCR biology in endocrinology and metabolism, as well as on GPCR-related endocrine diseases and drug discovery.

Knickkopf (LmKnk) is required for chitin organization in the foregut of Locusta migratoria.

The foregut, located at the front of the digestive tract, serves a vital role in insects by storing and grinding food into small particles. The innermost layer of the foregut known as the chitinous intima, comes into direct contact with the food and acts as a protective barrier against abrasive particles. Knickkopf (Knk) is required for chitin organization in the chitinous exoskeleton, tracheae and wings. Despite its significance, little is known about the biological function of Knk in the foregut. In this study, we found that LmKnk was stably expressed in the foregut, and highly expressed before molting in Locusta migratoria. To ascertain the biological function of LmKnk in the foregut, we synthesized specific double-stranded LmKnk (dsLmKnk) and injected it into locusts. Our findings showed a significant decrease in the foregut size, along with reduced food intake and accumulation of residues in the foregut after dsLmKnk injection. Morphological observations revealed that newly formed intima became thinner and lacked chitin lamella. Furthermore, fluorescence immunohistochemistry revealed that LmKnk was located in the apical region of new intima and epithelial cells. Taken together, this study provides insights into the biological function of LmKnk in the foregut, and identifies the potential target gene for exploring biological pest management strategies.

CGRP is essential for protection against alveolar epithelial cell necroptosis by activating the AMPK/L-OPA1 signaling pathway during acute lung injury.

Alveolar epithelial cell (AEC) necroptosis is critical to disrupt the alveolar barrier and provoke acute lung injury (ALI). Here, we define calcitonin gene-related peptide (CGRP), the most abundant endogenous neuropeptide in the lung, as a novel modulator of AEC necroptosis in lipopolysaccharide (LPS)-induced ALI. Upon LPS-induced ALI, overexpression of Cgrp significantly mitigates the inflammatory response, alleviates lung tissue damage, and decreases AEC necroptosis. Similarly, CGRP alleviated AEC necroptosis under the LPS challenge in vitro. Previously, we identified that long optic atrophy 1 (L-OPA1) deficiency mediates mitochondrial fragmentation, leading to AEC necroptosis. In this study, we discovered that CGRP positively regulated mitochondrial fusion through stabilizing L-OPA1. Mechanistically, we elucidate that CGRP activates AMP-activated protein kinase (AMPK). Furthermore, the blockade of AMPK compromised the protective effect of CGRP against AEC necroptosis following the LPS challenge. Our study suggests that CRGP-mediated activation of the AMPK/L-OPA1 axis may have potent therapeutic benefits for patients with ALI or other diseases with necroptosis.